Gaia Pocobelli

Body-mass index and mortality among 1.46 million white adults.

BACKGROUND A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. METHODS We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). RESULTS The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. CONCLUSIONS In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.

Tradeoffs between accuracy measures for electronic health care data algorithms.

OBJECTIVE We review the uses of electronic health care data algorithms, measures of their accuracy, and reasons for prioritizing one measure of accuracy over another. STUDY DESIGN AND SETTING We use real studies to illustrate the variety of uses of automated health care data in epidemiologic and health services research. Hypothetical examples show the impact of different types of misclassification when algorithms are used to ascertain exposure and outcome. RESULTS High algorithm sensitivity is important for reducing the costs and burdens associated with the use of a more accurate measurement tool, for enhancing study inclusiveness, and for ascertaining common exposures. High specificity is important for classifying outcomes. High positive predictive value is important for identifying a cohort of persons with a condition of interest but that need not be representative of or include everyone with that condition. Finally, a high negative predictive value is important for reducing the likelihood that study subjects have an exclusionary condition. CONCLUSION Epidemiologists must often prioritize one measure of accuracy over another when generating an algorithm for use in their study. We recommend researchers publish all tested algorithms-including those without acceptable accuracy levels-to help future studies refine and apply algorithms that are well suited to their objectives.

Use of Supplements of Multivitamins, Vitamin C, and Vitamin E in Relation to Mortality

In this cohort study, the authors evaluated how supplemental use of multivitamins, vitamin C, and vitamin E over a 10-year period was related to 5-year total mortality, cancer mortality, and cardiovascular disease (CVD) mortality. Participants (n = 77,719) were Washington State residents aged 50-76 years who completed a mailed self-administered questionnaire in 2000-2002. Adjusted hazard ratios and 95% confidence intervals were computed using Cox regression. Multivitamin use was not related to total mortality. However, vitamin C and vitamin E use were associated with small decreases in risk. In cause-specific analyses, use of multivitamins and use of vitamin E were associated with decreased risks of CVD mortality. The hazard ratio comparing persons who had a 10-year average frequency of multivitamin use of 6-7 days per week with nonusers was 0.84 (95% confidence interval: 0.70, 0.99); and the hazard ratio comparing persons who had a 10-year average daily dose of vitamin E greater than 215 mg with nonusers was 0.72 (95% confidence interval: 0.59, 0.88). In contrast, vitamin C use was not associated with CVD mortality. Multivitamin and vitamin E use were not associated with cancer mortality. Some of the associations we observed were small and may have been due to unmeasured healthy behaviors that were more common in supplement users.

Statin use and risk of breast cancer

Findings that statins inhibited the proliferation of breast cancer cells in vitro and in rodents have raised interest in whether the use of statins might decrease a womans risk of developing breast cancer. We analyzed data from a population‐based case‐control study to evaluate the association between the use of statins and breast cancer risk.

Administrative Data Algorithms to Identify Second Breast Cancer Events Following Early-Stage Invasive Breast Cancer

BACKGROUND Studies of breast cancer outcomes rely on the identification of second breast cancer events (recurrences and second breast primary tumors). Cancer registries often do not capture recurrences, and chart abstraction can be infeasible or expensive. An alternative is using administrative health-care data to identify second breast cancer events; however, these algorithms must be validated against a gold standard. METHODS We developed algorithms using data from 3152 women in an integrated health-care system who were diagnosed with stage I or II breast cancer in 1993-2006. Medical record review served as the gold standard for second breast cancer events. Administrative data used in algorithm development included procedures, diagnoses, prescription fills, and cancer registry records. We randomly divided the cohort into training and testing samples and used a classification and regression tree analysis to build algorithms for classifying women as having or not having a second breast cancer event. We created several algorithms for researchers to use based on the relative importance of sensitivity, specificity, and positive predictive value (PPV) in future studies. RESULTS The algorithm with high specificity and PPV had 89% sensitivity (95% confidence interval [CI] = 84% to 92%), 99% specificity (95% CI = 98% to 99%), and 90% PPV (95% CI = 86% to 94%); the high-sensitivity algorithm had 96% sensitivity (95% CI = 93% to 98%), 95% specificity (95% CI = 94% to 96%), and 74% PPV (95% CI = 68% to 78%). CONCLUSIONS Algorithms based on administrative data can identify second breast cancer events with high sensitivity, specificity, and PPV. The algorithms presented here promote efficient outcomes research, allowing researchers to prioritize sensitivity, specificity, or PPV in identifying second breast cancer events.

Hepatocellular carcinoma incidence trends in Canada: analysis by birth cohort and period of diagnosis

Background and Aims: We examined birth cohort and calendar period trends in hepatocellular carcinoma (HCC) incidence in Canada (1976–2000). We also projected HCC incidence rates through 2015.

Long-Term Use of Supplemental Vitamins and Minerals Does Not Reduce the Risk of Urothelial Cell Carcinoma of the Bladder in the VITamins And Lifestyle Study

PURPOSE Urothelial carcinoma has the highest lifetime treatment cost of any cancer, making it an ideal target for preventative therapies. Previous work has suggested that certain vitamin and mineral supplements may reduce the risk of urothelial carcinoma. We used the prospective VITamins And Lifestyle cohort to examine the association of all commonly taken vitamin and mineral supplements as well as 6 common anti-inflammatory supplements with incident urothelial carcinoma in a United States population. MATERIALS AND METHODS A total of 77,050 eligible VITAL participants completed a detailed questionnaire at baseline on supplement use and cancer risk factors. After 6 years of followup 330 incident urothelial carcinoma cases in the cohort were identified via linkage to the Seattle-Puget Sound SEER cancer registry. We analyzed use of supplemental vitamins (multivitamins, beta-carotene, retinol, folic acid, and vitamins B1, B3, B6, B12, C, D and E), minerals (calcium, iron, magnesium, zinc and selenium) and anti-inflammatory supplements (glucosamine, chondroitin, saw palmetto, ginkgo biloba, fish oil and garlic). For each supplement the hazard ratios (risk ratios) for urothelial carcinoma comparing each category of users to nonusers, and 95% CIs, were determined using Cox proportional hazards regression, adjusted for potential confounders. RESULTS None of the vitamin, mineral or anti-inflammatory supplements was significantly associated with urothelial carcinoma risk in age adjusted or multivariate models. CONCLUSIONS The results of this study do not support the use of commonly taken vitamin or mineral supplements or 6 common anti-inflammatory supplements for the chemoprevention of urothelial carcinoma.

Variability in mitotic figures in serial sections of thin melanomas

BACKGROUND T1 melanoma staging is significantly affected by tissue sampling approaches, which have not been well characterized. OBJECTIVE We sought to characterize presence of mitotic figures across a minimum of 5 sequential sections of T1 melanomas. METHODS A cohort of T1 melanomas with either 5 (single section per slide) or 10 (2 sections per slide) sequential sections (5-μm thickness) per case were prepared and examined for mitotic figures. RESULTS In all, 44 of 82 T1 melanomas (54%) were classified as T1b. The number of sections with a mitotic figure present ranged from only 1 of 5 sections (n = 5 of 44 cases, 11.4%) to all 5 (n = 20 of 44 cases, 45.5%). A sequential approach versus a nonsequential approach did not appear to matter. LIMITATION Cases were taken from a single pathology practice in the Pacific Northwest, which may not generalize to other populations in the United States. CONCLUSION The variation in the presence of mitotic figures within sequential sections supports reviewing 3 to 5 sections to fulfill American Joint Committee on Cancer recommendations. The prognostic significance of a T1b melanoma with a rare mitotic figure on a single section versus a T1b melanoma with mitotic figures on multiple sections deserves more attention to see if further subclassification is possible or even necessary.

Pregnancy history and risk of endometrial cancer.

Background: Epidemiologic studies are consistent in finding that women who have had at least one birth are less likely to develop endometrial cancer. Less clear is whether timing of pregnancies during reproductive life influences risk, and the degree to which incomplete pregnancies are associated with a reduced risk. Methods: We evaluated pregnancy history in relation to endometrial cancer risk using data from a series of 4 population-based endometrial cancer case-control studies of women 45–74 years of age (1712 cases and 2134 controls) during 1985–2005 in western Washington State. Pregnancy history and information on other potential risk factors were collected by in-person interviews. Results: Older age at first birth was associated with a reduced risk of endometrial cancer after adjustment for number of births and age at last birth (test for trend P = 0.004). The odds ratio comparing women at least 35 years of age at their first birth with those younger than 20 years was 0.34 (95% confidence interval = 0.14–0.84). Age at last birth was not associated with risk after adjustment for number of births and age at first birth (test for trend P = 0.830). Overall, a history of incomplete pregnancies was not associated with endometrial cancer risk to any appreciable degree. Conclusions: In this study, older age at first birth was more strongly associated with endometrial cancer risk than was older age at last birth. To date, there remains some uncertainty in the literature on this issue.

Prophylactic oophorectomy rates in relation to a guideline update on referral to genetic counseling

OBJECTIVE We sought to determine whether prophylactic oophorectomy rates changed after the introduction of a 2007 health plan clinical guideline recommending systematic referral to a genetic counselor for women with a personal or family history suggestive of an inherited susceptibility to breast/ovarian cancer. METHODS We conducted a retrospective cohort study of female members of Group Health, an integrated delivery system in Washington State. Subjects were women aged ≥ 35 years during 2004-2009 who reported a personal or family history consistent with an inherited susceptibility to breast/ovarian cancer. Personal and family history information was collected on a questionnaire completed when the women had a mammogram. We ascertained oophorectomies from automated claims data and determined whether surgeries were prophylactic by medical chart review. Rates were age-adjusted and age-adjusted incidence rate ratios (IRR) and 95% confidence intervals (CI) were computed using Poisson regression. RESULTS Prophylactic oophorectomy rates were relatively unchanged after compared to before the guideline change, 1.0 versus 0.8/1000 person-years, (IRR=1.2; 95% CI: 0.7-2.0), whereas bilateral oophorectomy rates for other indications decreased. Genetic counseling receipt rates doubled after the guideline change (95% CI: 1.7-2.4) from 5.1 to 10.2/1000 person-years. During the study, bilateral oophorectomy rates were appreciably greater in women who saw a genetic counselor compared to those who did not regardless of whether they received genetic testing as part of their counseling. CONCLUSION A doubling in genetic counseling receipt rates lends support to the idea that the guideline issuance contributed to sustained rates of prophylactic oophorectomies in more recent years.